Role of ADAMTS1 in the development of uveal melanoma

Scientists from the University of Granada and GENYO, Spain, have demonstrated the role of a protein called ADAMTS1 in the development of uveal melanoma, one of the rarest and most aggressive cancers.

Uveal melanoma is a rare cancer that develops in the eye and leads to metastasis in 50% of patients, with an incidence of 2–8 cases per million inhabitants in Europe. As published in Cancers, scientists from the University of Granada and GENYO (Pfizer-University of Granada-Andalusian Government Centre for Genomics and Oncological Research) have demonstrated the significant role of a protein called ADAMTS1 in uveal melanoma.

Tumours are composed of cells that grow uncontrollably and an environment they create during their growth, also known as the ‘tumour microenvironment’. Within this environment, there are proteins that remodel it, known as extracellular proteases, which are capable of inhibiting or contributing to tumour growth and metastasis. They do this by modifying non-cellular elements of the tumour microenvironment that form the so-called extracellular matrix.

In a study led by Juan Carlos Rodríguez-Manzaneque, a group leader at GENYO, the researchers studied the role that one of these proteases, ADAMTS1, plays in the development of a rare and highly-aggressive subtype of melanoma: uveal melanoma.

Carlos Peris Torres, the main author of the paper, explains: “In this research, we demonstrated that the ADAMTS1 protease is necessary for cancer cells to mimic endothelial cells (responsible for forming blood vessels), which is related to more aggressive tumours and a worse clinical prognosis.”

Weaponising tumour genetics to fight uveal melanoma

The researchers inhibited the ADAMTS1 protease using CRISPR/Cas9 gene-editing technology. This is a molecular tool used to ‘edit’ or ‘correct’ the genome of any cell. The researchers then verified the outcomes of their intervention on the protease in in vitro models with cell lines, and in vivo with different mouse models.

In addition, using advanced bioinformatic tools and publicly-available data on uveal melanomas, the University of Granada and GENYO scientists found new genes whose expression affects the clinical prognosis of this tumour type.

In light of these results, the researchers have concluded that ADAMTS1 is necessary for the development of uveal melanoma. This study is also the first to support the development of therapeutic targets aimed at the extracellular matrix to combat uveal melanoma.

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